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Chemical Compound Review:

BSPBio_001450 2-[[(2R)-2-acetyloxy-3- octadecoxy-propoxy]...

Synonyms: KBioGR_000170, KBioSS_000170, CHEBI:52450, CBiol_001781, AC1MBZ4I, ...

Ring, P.C. et al., Gomez, J. et al., Handa, R.K. et al., Toga, H. et al., Schwinger, R.H. et al., et al.

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Disease relevance of PAF acether

Bolus injections of C16-PAF (0.5-25 ng/kg) and C18-PAF (2.5-200 ng/kg) into the arterial circulation of the kidney produced increases in renal blood flow (6-15%) before causing dose-dependent systemic hypotension (2-64 mmHg) [1].

High impact information on PAF acether

Ether lipid analogues of platelet-activating factor (1-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) possess a wide range of biological activities, including inhibition of neoplastic cell growth in vitro and in vivo [2].
3. In competition studies C18-PAF inhibited in a biphasic manner the binding of [3H]apafant to intact macrophages, which could be resolved into high (pKi = 8.27; 60%) and low (pKi = 6.06; 40%) affinity components [3].
In macrophage membranes, the affinity of C18-PAF (pKi = 8.48) determined from competition studies with [3H]apafant was significantly reduced (pKi = 6.95) by guanosine-5'-O-(3-thio)triphosphate, whereas the mean slope of the inhibition curves was increased from 0.470 to 0.700 [3].
Pretreatment of macrophages with apafant antagonized in a noncompetitive manner the first phase of C18-PAF (< 100 nM)-induced respiratory burst, whereas the second component (> 1 microM C18-PAF) of this response was unaffected [3].
These results indicate that guinea pig lung has specific binding sites for [3H]C16-PAF, that WEB 2086 is an effective antagonist of C16- and C18-PAF binding at these sites, and that RP52770 binds to the PAF site but, in addition, binds to another site with a much greater density [4].

Biological context of PAF acether

Compound 6 shows reduced platelet aggregation and hypotensive activity in comparison with C16 and C18 PAF [5].
C18-PAF constricted both upstream and venous segments of the pulmonary circulation [6].
The dose-response curves for renal blood flow and systemic blood pressure generated by intrarenal C18-PAF administration were approximately 7 fold to the right of the dose-response curves generated by C16-DPAF [1].
We investigated whether exogenous PAF could specifically stimulate embryonic cell proliferation prior to the blastocyst stage in the mouse and also compared the biological activities of the C16 and C18 PAF isoforms as follows [7].

Anatomical context of PAF acether

PAF (C16-PAF, C18-PAF; 0.000001 to 1 mumol/L) had no effect on isometric force of contraction of electrically driven right atrial trabeculae (patients undergoing aortocoronary bypass surgery) and left ventricular papillary muscle strips (mitral valve replacement) [8].
The present study has examined the catabolism of 1-O-[3H]hexadecyl-2-acetyl-GPC (C16-PAF) and of 1-O-octadecyl-2-acetyl-GPC (C18-PAF) in spleen-derived PT-18 murine mast cells (mast cells) [9].

Associations of PAF acether with other chemical compounds

Direct binding studies with [3H]RP52770 revealed a much larger density of binding sites (1,200 fmol/mg protein), and this binding was not inhibited with C16-PAF, C18-PAF, WEB 2086, or lyso-PAF [4].

Analytical, diagnostic and therapeutic context of PAF acether

Cyclooxygenase inhibition in isolated lungs attenuated arterial constriction to C18-PAF, whereas simultaneous cyclooxygenase and lipoxygenase inhibition completely blocked the effects of C18-PAF [6].
In addition, the elution times of phospholipase C digestion of C18 PAF and the neutral lipid produced by cellular metabolism of [3H]PAF, determined by gas chromatography/flame ionization detection, were similar [10].

References

Vasorelaxant effect of C16-PAF and C18-PAF on renal blood flow and systemic blood pressure in the anesthetized rat. Handa, R.K., Strandhoy, J.W., Buckalew, V.M. Life Sci. (1991) [Pubmed]
In vitro antiproliferative activity of combinations of ether lipid analogues and DNA-interactive agents against human tumor cells. Noseda, A., Berens, M.E., White, J.G., Modest, E.J. Cancer Res. (1988) [Pubmed]
Pharmacological characterization of a receptor for platelet-activating factor on guinea pig peritoneal macrophages using [3H]apafant, a selective and competitive platelet-activating factor antagonist: evidence that the noncompetitive behavior of apafant in functional studies relates to slow kinetics of dissociation. Ring, P.C., Seldon, P.M., Barnes, P.J., Giembycz, M.A. Mol. Pharmacol. (1993) [Pubmed]
Characterization of receptors for platelet-activating factor in guinea pig lung membranes. Gomez, J., Bloom, J.W., Yamamura, H.I., Halonen, M. Am. J. Respir. Cell Mol. Biol. (1990) [Pubmed]
Analogues of platelet activating factor (PAF). 1. Some modifications of the alkoxy chain. Wissner, A., Sum, P.E., Schaub, R.E., Kohler, C.A., Goldstein, B.M. J. Med. Chem. (1984) [Pubmed]
Vascular effects of platelet-activating factor in lambs: role of cyclo- and lipoxygenase. Toga, H., Hibler, S., Ibe, B.O., Raj, J.U. J. Appl. Physiol. (1992) [Pubmed]
Exogenous platelet-activating factor stimulates cell proliferation in mouse pre-implantation embryos prior to the fourth cell cycle and shows isoform-specific stimulatory effects. Stoddart, N.R., Roudebush, W.E., Fleming, S.D. Zygote (2001) [Pubmed]
Existence of PAF receptors in human platelets and human lung tissue but not in the human myocardium. Schwinger, R.H., Böhm, M., La Rosée, K., Erdmann, E. Am. Heart J. (1992) [Pubmed]
Influence of immunologic activation and cellular fatty acid levels on the catabolism of platelet-activating factor within the murine mast cell (PT-18). Triggiani, M., Chilton, F.H. Biochim. Biophys. Acta (1989) [Pubmed]
Differential metabolism of exogenous platelet-activating factor by glandular epithelial and stromal cells of rabbit endometrium. Kudolo, G.B., Yang, Y.Q., Chen, D.B., Jones, M.A., Harper, M.J. J. Reprod. Fertil. (1995) [Pubmed]

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